Ras involvement in signal transduction by the serotonin 5-HT2B receptor.

The family of serotonin 5-HT2 receptors stimulates the phospholipase C second messenger pathway via the alpha subunit of the Gq GTP-binding protein. Here, we show that agonist stimulation of the 5-HT2B receptor subtype stably expressed in the mouse fibroblast LMTK- cell line causes a rapid and transient activation of the ...
proto-oncogene product p21ras as measured by an increase in GTP-bound Ras in response to serotonin. Furthermore, 5-HT2B receptor stimulation activates p42mapk/p44mapk (ERK2/ERK1) mitogen-activated protein kinases as assayed by phosphorylation of myelin basic protein. Antibodies against p21ras, Galphaq, -beta, or -gamma2 subunits of the GTP-binding protein inhibit MAP kinase-dependent phosphorylation. The MAP kinase activation is correlated with a stimulation of cell division by serotonin. In addition to this mitogenic action, transforming activity of serotonin is mediated by the 5-HT2B receptor since its expression in LMTK- cells is absolutely required for foci formation and for these foci to form tumors in nude mice. Finally, we detected expression of the 5-HT2B receptor in spontaneous human and Mastomys natalensis carcinoid tumors and, similar to the 5-HT2B receptor transfected cells, the Mastomys tumor cells are also responsive to serotonin with similar coupling to p21ras activation.
Mesh Terms:
Amphetamines, Animals, Carcinoid Tumor, Cell Line, Enzyme Activation, GTP Phosphohydrolases, GTP-Binding Proteins, Gene Expression, Humans, Immunohistochemistry, Kinetics, Mice, Muridae, Receptor, Serotonin, 5-HT2B, Receptors, Serotonin, Recombinant Proteins, Ritanserin, Rodent Diseases, Second Messenger Systems, Serotonin, Serotonin Agonists, Signal Transduction, Transfection, Type C Phospholipases, ras Proteins
J. Biol. Chem.
Date: Feb. 09, 1996
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